title: Therapeutic role of EF24 targeting glucose transporter 1-mediated metabolism and metastasis in ovarian cancer cells.
abstract: Cancer cells require glucose to support their rapid growth through a process known as aerobic glycolysis, or the Warburg effect. As in ovarian cancer cells, increased metabolic activity and glucose concentration has been linked to aggressiveness of cancer. However, it is unclear as to whether targeting the glycolytic pathway may kill the malignant cells and likely have broad therapeutic implications against ovarian cancer metastasis. In the present research, we found that EF24, a HIF-1α inhibitor, could significantly block glucose uptake, the rate of glycolysis, and lactate production compared with vehicle treatment in SKOV-3, A2780 and OVCAR-3 cells. These results might possibly contribute to the further observation that EF24 could inhibit ovarian cancer cell migration and invasion from wound healing and Transwell assays. Furthermore, as an important mediator of glucose metabolism, glucose transporter 1 (Glut1) was found to contribute to the function of EF24 in both energy metabolism and metastasis. To examine the effect of EF24 and the mediated role of Glut1 in vivo in a xenograph subcutaneous tumor model, intraperitoneal metastasis and lung metastasis model were introduced. Our results indicated that EF24 treatment could inhibit tumor growth, intraperitoneal metastasis and lung metastasis of SKOV-3 cells, and Glut1 is a possible mediator for the role of EF24. In conclusion, our results highlight that an anti-cancer reagent with an inhibiting effect on energy metabolism could inhibit metastasis, and EF24 is a possible candidate for anti-metastasis therapeutic applications for ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Lina
authors.initials: L
authors.lastname: Dong
authors.forename: Yangang
authors.initials: Y
authors.lastname: Huang
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.forename: Wei
authors.initials: W
authors.lastname: Ben
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Ning
authors.initials: N
authors.lastname: Ning
authors.forename: Meisong
authors.initials: M
authors.lastname: Lu
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Guan
mesh_terms: D000818:Animals; D001597:Benzylidene Compounds / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors; D019344:Lactic Acid / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000556:secondary; D010881:Piperidones / Q000494:pharmacology*
chemical_list: C524042:3,5-bis(2-fluorobenzylidene)piperidin-4-one; D001597:Benzylidene Compounds; D051272:Glucose Transporter Type 1; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010881:Piperidones; C495677:SLC2A1 protein, human; D019344:Lactic Acid; D005947:Glucose